Development of a Clinically Viable Heroin Vaccine

Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and...

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Published inJournal of the American Chemical Society Vol. 139; no. 25; pp. 8601 - 8611
Main Authors Bremer, Paul T, Schlosburg, Joel E, Banks, Matthew L, Steele, Floyd. F, Zhou, Bin, Poklis, Justin L, Janda, Kim D
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 28.06.2017
Amer Chemical Soc
Subjects
adjuvants
Adjuvants, Immunologic - chemistry
alum
antibodies
antiserum
Chemistry
Chemistry, Multidisciplinary
cross reaction
Drug Design
haptens
Haptens - chemistry
Heroin
Immunity, Humoral
immunization
immunoglobulin G
Macaca mulatta
metabolites
mice
monkeys
narcotics
oligodeoxyribonucleotides
Physical Sciences
Science & Technology
surface plasmon resonance
vaccines
Vaccines, Conjugate
NONHUMAN-PRIMATES
SMOKING-CESSATION
THERAPEUTIC COCAINE VACCINE
CONJUGATE VACCINE
RHESUS-MONKEYS
DOUBLE-BLIND
PLACEBO-CONTROLLED TRIAL
ACTIVE IMMUNIZATION
CONTROLLED EFFICACY-TRIAL
ANTI-NICOTINE VACCINE
Online AccessGet full text
ISSN0002-7863
1520-5126
1520-5126
DOI10.1021/jacs.7b03334

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Abstract Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin “immunoantagonism”, reducing heroin potency by >15-fold. Moreover, the vaccine effects proved to be durable, persisting for over eight months. The lead vaccine was effective in rhesus monkeys, generating significant and sustained antidrug IgG titers in each subject. Characterization of both mouse and monkey antiheroin antibodies by surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity for the key heroin metabolite, 6-acetylmorphine (6AM), with minimal cross reactivity to clinically used opioids. Following a series of heroin challenges over six months in vaccinated monkeys, drug-sequestering antibodies caused marked attenuation of heroin potency (>4-fold) in a schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide an empirical foundation supporting the further evaluation and potential clinical utility of an effective heroin vaccine in treating opioid use disorders.
AbstractList Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin immunoantagonism, reducing heroin potency by >15-fold. Moreover, the vaccine effects proved to be durable, persisting for over eight months. The lead vaccine was effective in rhesus monkeys, generating significant and sustained antidrug IgG titers in each subject. Characterization of both mouse and monkey antiheroin antibodies by surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity for the key heroin metabolite, 6-acetylmorphine (6AM), with minimal cross reactivity to clinically used opioids. Following a series of heroin challenges over six months in vaccinated monkeys, drug-sequestering antibodies caused marked attenuation of heroin potency (>4-fold) in a schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide an empirical foundation supporting the further evaluation and potential clinical utility of an effective heroin vaccine in treating opioid use disorders.
Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin ‘immunoantagonism’, reducing heroin potency by >15-fold. Moreover, the vaccine effects proved to be durable, persisting for over eight months. The lead vaccine was effective in rhesus monkeys, generating significant and sustained anti-drug IgG titers in each subject. Characterization of both mouse and monkey anti-heroin antibodies by surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity for the key heroin metabolite, 6-acetylmorphine (6AM), with minimal cross reactivity to clinically-used opioids. Following a series of heroin challenges over six months in vaccinated monkeys, drug-sequestering antibodies caused marked attenuation of heroin potency (>4-fold) in a schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide an empirical foundation supporting the further evaluation and potential clinical utility of an effective heroin vaccine in treating opioid use disorders.
Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin "immunoantagonism", reducing heroin potency by >15-fold. Moreover, the vaccine effects proved to be durable, persisting for over eight months. The lead vaccine was effective in rhesus monkeys, generating significant and sustained antidrug IgG titers in each subject. Characterization of both mouse and monkey antiheroin antibodies by surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity for the key heroin metabolite, 6-acetylmorphine (6AM), with minimal cross reactivity to clinically used opioids. Following a series of heroin challenges over six months in vaccinated monkeys, drug-sequestering antibodies caused marked attenuation of heroin potency (>4-fold) in a schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide an empirical foundation supporting the further evaluation and potential clinical utility of an effective heroin vaccine in treating opioid use disorders.Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin "immunoantagonism", reducing heroin potency by >15-fold. Moreover, the vaccine effects proved to be durable, persisting for over eight months. The lead vaccine was effective in rhesus monkeys, generating significant and sustained antidrug IgG titers in each subject. Characterization of both mouse and monkey antiheroin antibodies by surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity for the key heroin metabolite, 6-acetylmorphine (6AM), with minimal cross reactivity to clinically used opioids. Following a series of heroin challenges over six months in vaccinated monkeys, drug-sequestering antibodies caused marked attenuation of heroin potency (>4-fold) in a schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide an empirical foundation supporting the further evaluation and potential clinical utility of an effective heroin vaccine in treating opioid use disorders.
Author Zhou, Bin
Poklis, Justin L
Schlosburg, Joel E
Janda, Kim D
Bremer, Paul T
Banks, Matthew L
Steele, Floyd. F
AuthorAffiliation Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology
Department of Pharmacology and Toxicology
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– name: 1 Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Roadd, La Jolla, CA 92037, USA
– name: 2 Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/28574716$$D View this record in MEDLINE/PubMed
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Issue 25
Keywords NONHUMAN-PRIMATES
SMOKING-CESSATION
THERAPEUTIC COCAINE VACCINE
CONJUGATE VACCINE
RHESUS-MONKEYS
DOUBLE-BLIND
PLACEBO-CONTROLLED TRIAL
ACTIVE IMMUNIZATION
CONTROLLED EFFICACY-TRIAL
ANTI-NICOTINE VACCINE
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  day: 28
PublicationDecade 2010
PublicationPlace WASHINGTON
PublicationPlace_xml – name: WASHINGTON
– name: United States
PublicationTitle Journal of the American Chemical Society
PublicationTitleAbbrev J AM CHEM SOC
PublicationTitleAlternate J. Am. Chem. Soc
PublicationYear 2017
Publisher American Chemical Society
Amer Chemical Soc
Publisher_xml – name: American Chemical Society
– name: Amer Chemical Soc
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Snippet Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid...
Source Web of Science
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pubmed
webofscience
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acs
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StartPage 8601
SubjectTerms adjuvants
Adjuvants, Immunologic - chemistry
alum
antibodies
antiserum
Chemistry
Chemistry, Multidisciplinary
cross reaction
Drug Design
haptens
Haptens - chemistry
Heroin
Immunity, Humoral
immunization
immunoglobulin G
Macaca mulatta
metabolites
mice
monkeys
narcotics
oligodeoxyribonucleotides
Physical Sciences
Science & Technology
surface plasmon resonance
vaccines
Vaccines, Conjugate
Title Development of a Clinically Viable Heroin Vaccine
URI http://dx.doi.org/10.1021/jacs.7b03334
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=000404809600035
https://www.ncbi.nlm.nih.gov/pubmed/28574716
https://www.proquest.com/docview/1905734629
https://www.proquest.com/docview/2116874897
https://pubmed.ncbi.nlm.nih.gov/PMC5612493
Volume 139
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